Bio

Honors & Awards


  • Eidgenössische Stipendienkommission für ausländische Studierende (ESKAS), Suisse Federal Commision, Berne (2006-2008)
  • ORS Award, UK, http://www.orsas.ac.uk/ (2009-2011)
  • European Stroke Organization Award, SITS-ISTR, Dept of Neurology, Karolinska University, Sweden. (2009)
  • Travel grant of the IHS Trainee and Residents, Sub-committee for the European Headache and Migraine Trust International Congress, London. (2008)
  • Department of Medicine and Therapeutics Tuition Support, Faculty of Medicine, University of Glasgow (2008-2009)
  • Jim Gatheral Scholarship, Clinical Research Fellow at UT Houston, Texas (2011)
  • Roberts Travel fellowship, University of Glasgow, UK (2009)
  • University Studentship Award, University of Glasgow (2008-2011)
  • Ratan Tata Trust Scholarship, Tata Trust, Mumbai (2003)

Boards, Advisory Committees, Professional Organizations


  • Fellow, European Stroke Organization (2012 - Present)
  • Member, European Stroke Organization (2009 - Present)
  • Member, World Stroke Organization (2006 - Present)
  • Member, Stroke Council, American Heart Association (2014 - Present)

Professional Education


  • MBBS (MD), Maharshtra University of Health Sciences, Nashik, India, Medicine (2005)
  • Alliance Française, Vorbereitungskurse auf das Hochschulstudium in der Schweiz, Université de Fribourg, Switzerland, French (2006)
  • Clinical Fellowship, CHUV, Service de Neurologie, Universite de Lausanne, Switzerland, Neurology: Stroke and Behavioral Neurology (2008)
  • PhD (Medicine and Therapeutics), Cardiovascular Medicine, Western Infirmary and Faculty of Medicine, University of Glasgow, Scotland., Use of thrombolytic therapy beyond current recommendations in acute ischemic stroke (2012)

Research & Scholarship

Current Research and Scholarly Interests


1. Use of brain imaging in the selection of ischemic stroke patients for reperfusion therapy.
2. Thrombolytic therapy in acute ischemic stroke.
3. Clinical Research: Outcomes research, mathematical modelling, and study design.
4. Evidence based medicine: systematic reviews and meta-analysis.
5. Impact of ethnicity on outcomes in stroke patients.

Publications

Journal Articles


  • Comparison of Magnetic Resonance Imaging Mismatch Criteria to Select Patients for Endovascular Stroke Therapy. Stroke; a journal of cerebral circulation Mishra, N. K., Albers, G. W., Christensen, S., Marks, M., Hamilton, S., Straka, M., Liggins, J. T., Kemp, S., Mlynash, M., Bammer, R., Lansberg, M. G. 2014

    Abstract

    The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study has shown that clinical response to endovascular reperfusion differs between patients with and without perfusion-diffusion (perfusion-weighted imaging-diffusion-weighted imaging, PWI-DWI) mismatch: patients with mismatch have a favorable clinical response to reperfusion, whereas patients without mismatch do not. This study examined whether alternative mismatch criteria can also differentiate patients according to their response to reperfusion.Patients from the DEFUSE 2 study were categorized according to vessel occlusion on magnetic resonance angiography (MRA) and DWI lesion volume criteria (MRA-DWI mismatch) and symptom severity and DWI criteria (clinical-DWI mismatch). Favorable clinical response was defined as an improvement of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS) by day 30 or an NIHSS score of ≤1 at day 30. We assessed, for each set of criteria, whether the association between reperfusion and favorable clinical response differed according to mismatch status.A differential response to reperfusion was observed between patients with and without MRA-DWI mismatch defined as an internal carotid artery or M1 occlusion and a DWI lesion <50 mL. Reperfusion was associated with good functional outcome in patients who met these MRA-DWI mismatch criteria (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.3-31.3), whereas no association was observed in patients who did not meet these criteria (OR, 0.5; 95% CI, 0.08-3.1; P for difference between the odds, 0.01). No differential response to reperfusion was observed with other variations of the MRA-DWI or clinical-DWI mismatch criteria.The MRA-DWI mismatch is a promising alternative to DEFUSE 2's PWI-DWI mismatch for patient selection in endovascular stroke trials.

    View details for DOI 10.1161/STROKEAHA.114.004772

    View details for PubMedID 24699054

  • Postthrombolysis outcomes in acute ischemic stroke patients of Asian race-ethnicity. International journal of stroke Mishra, N. K., Chan, B. P., Teoh, H., Meng, C., Lees, K. R., Chen, C., Sharma, V. K. 2013; 8: 95-99

    Abstract

    BACKGROUND: Race-ethnic differences may influence postthrombolysis outcomes in acute ischemic stroke patients. Guidelines for thrombolytic therapy to treat Asian stroke patients are based mostly on extrapolated western data. AIMS: We undertook to examine outcomes among Asians by comparing a propensity-matched cohort of thrombolyzed patients from a tertiary center in Singapore with nonthrombolyzed Asian comparators collated from Virtual International Stroke Trials Archives (control). METHODS: We identified propensity scores-matched patients between thrombolyzed and control Asian patients lodged in the Virtual International Stroke Trials Archives by employing propensity scores method. We compared matched patients for their distributions of three-month functional (modified Rankin scores) and neurological outcomes (National Institute of Health Stroke Scale) by employing Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis. We report odds ratio and 95% confidence interval for improved outcomes on day 90. RESULTS: Virtual International Stroke Trials Archives and National University Hospital, Singapore, contributed 517 and 133 patients of Asian race-ethnicity (n = 650), respectively. After propensity matching, sample size reduced to 237 patients; 104 were from Virtual International Stroke Trials Archives. Age (59·7 vs. 61·5 years, P = 0·2) and mean baseline National Institute of Health Stroke Scale scores were similar (14) between thrombolyzed and control. The odds ratio for shift toward improved modified Rankin scores and National Institute of Health Stroke Scale distributions after tissue plasminogen activator therapy were 2·8 (95% confidence interval 1·8-4·5, P < 0·0001, n = 233; Cochran-Mantel-Haenszel P < 0·0001) and 2·8 (95% confidence interval 1·7-4·7, P = 0·0008, n = 201; Cochran-Mantel-Haenszel P = 0·0001). CONCLUSIONS: Our data indicate that Asian patients derive benefit from thrombolytic therapy.

    View details for DOI 10.1111/ijs.12012

    View details for PubMedID 23490069

  • The Modified Graeb Score An Enhanced Tool for Intraventricular Hemorrhage Measurement and Prediction of Functional Outcome STROKE Morgan, T. C., Dawson, J., Spengler, D., Lees, K. R., Aldrich, C., Mishra, N. K., Lane, K., Quinn, T. J., Diener-West, M., Weir, C. J., Higgins, P., Rafferty, M., Kinsley, K., Ziai, W., Awad, I., Walters, M. R., Hanley, D. 2013; 44 (3): 635-641

    Abstract

    Simple and rapid measures of intraventricular hemorrhage (IVH) volume are lacking. We developed and validated a modification of the original Graeb scale to facilitate rapid assessment of IVH over time.We explored the relationship between the modified Graeb scale (mGS), original Graeb scale, measured IVH volume, and outcome using data from the Clot Lysis: Evaluating Accelerated Resolution of Hemorrhage with rtPA B (CLEAR B) study. We also explored its reliability. We then evaluated the relationship between mGS and outcome in a large sample of participants with IVH using data contained within the Virtual International Stroke Trials Archive (VISTA). We defined outcome using the modified Rankin scale (>3 signifying poor outcome).The CLEAR B study included 360 scans from 36 subjects. The mGS score and IVH volume were highly correlated (R = 0.80, P<0.0001, R(2) 0.65). Baseline mGS was predictive of poor outcome (area under receiving operating characteristic curve 0.74, 95% confidence interval, 0.57-0.91), whereas the original Graeb scale was not. The VISTA study included 399 participants. Each unit increase in the mGS led to a 12% increase in the odds of a poor outcome (odds ratio, 1.12; 95% confidence interval, 1.05-1.19). Measures of reliability (intra- and inter- reader) were good in both studies.The mGS, a semiquantitative scale for IVH volume measurement, is a reliable measure with prognostic validity suitable for rapid use in clinical practice and in research.

    View details for DOI 10.1161/STROKEAHA.112.670653

    View details for Web of Science ID 000315447400016

    View details for PubMedID 23370203

  • Thrombolysis in Stroke Despite Contraindications or Warnings? STROKE Frank, B., Grotta, J. C., Alexandrov, A. V., Bluhmki, E., Lyden, P., Meretoja, A., Mishra, N. K., Shuaib, A., Wahlgren, N. G., Weimar, C., Lees, K. R. 2013; 44 (3): 727-733

    Abstract

    Intravenous thrombolysis with alteplase is approved for acute ischemic stroke, but its use is limited by numerous contraindications and warnings arising from trial selection criteria or expert opinions. We examined outcomes from alteplase-treated versus untreated patients, registered in a trials archive, according to presence or absence of specified contraindications and warnings.We analyzed 90-day modified Rankin Scale across the whole distribution of scores using the Cochran-Mantel-Haenszel test, with adjustment for age and baseline National Institutes of Health Stroke Score, followed by proportional odds logistic regression analysis to estimate the odds ratios for preferred outcome.We used data from 9613 ischemic stroke patients of whom 2755 were treated with thrombolysis. Adjusted odds ratios showed a broad trend of more favorable 3-month outcome associated with alteplase treatment versus no treatment in various subgroups of patients with contraindications and warnings; for example, 1.40 (95% confidence interval [CI], 1.14-1.70) in patients aged >80 (n=1805), 1.50 (95% CI, 1.03-2.18) in patients with combined history of prior stroke and diabetes mellitus (n=672), 1.42 (95% CI, 1.19-1.70) in patients on prior single antiplatelet agent (n=1626), 2.20 (95% CI, 1.12-4.32) in patients on oral anticoagulation, and International Normalized Ratio?1.7 (n=157), 1.50 (95% CI, 1.15-1.97) in patients with baseline glucose >180 (n=879), and 1.57 (95% CI, 1.12-2.18) in patients with pretreatment National Institutes of Health Stroke Score >22 (n=620).This comprehensive retrospective analysis of various contraindications and warnings provides reassurance about benefits and risks of intravenous alteplase treatment in common clinical situations.

    View details for DOI 10.1161/STROKEAHA.112.674622

    View details for Web of Science ID 000315447400031

    View details for PubMedID 23391774

  • A score based on age and DWI volume predicts poor outcome following endovascular treatment for acute ischemic stroke. International journal of stroke : official journal of the International Stroke Society Liggins, J. T., Yoo, A. J., Mishra, N. K., Wheeler, H. M., Straka, M., Leslie-Mazwi, T. M., Chaudhry, Z. A., Kemp, S., Mlynash, M., Bammer, R., Albers, G. W., Lansberg, M. G. 2013

    Abstract

    The Houston Intra-Arterial Therapy score predicts poor functional outcome following endovascular treatment for acute ischemic stroke based on clinical variables. The present study sought to (a) create a predictive scoring system that included a neuroimaging variable and (b) determine if the scoring systems predict the clinical response to reperfusion.Separate datasets were used to derive (n = 110 from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 study) and validate (n = 125 from Massachusetts General Hospital) scoring systems that predict poor functional outcome, defined as a modified Rankin Scale score of 4-6 at 90 days.Age (P < 0·001; β = 0·087) and diffusion-weighted imaging volume (P = 0·023; β = 0·025) were the independent predictors of poor functional outcome. The Stanford Age and Diffusion-Weighted Imaging score was created based on the patient's age (0-3 points) and diffusion-weighted imaging lesion volume (0-1 points). The percentage of patients with a poor functional outcome increased significantly with the number of points on the Stanford Age and Diffusion-Weighted Imaging score (P < 0·01 for trend). The area under the receiver operating characteristic curve for the Stanford Age and Diffusion-Weighted Imaging score was 0·82 in the derivation dataset. In the validation cohort, the area under the receiver operating characteristic curve was 0·69 for the Stanford Age and Diffusion-Weighted Imaging score and 0·66 for the Houston Intra-Arterial Therapy score (P = 0·45 for the difference). Reperfusion, but not the interactions between the prediction scores and reperfusion, were predictors of outcome (P > 0·5).The Stanford Age and Diffusion-Weighted Imaging and Houston Intra-Arterial Therapy scores can be used to predict poor functional outcome following endovascular therapy with good accuracy. However, these scores do not predict the clinical response to reperfusion. This limits their utility as tools to select patients for acute stroke interventions.

    View details for DOI 10.1111/ijs.12207

    View details for PubMedID 24207136

  • Influence of racial differences on outcomes after thrombolytic therapy in acute ischemic stroke. International journal of stroke : official journal of the International Stroke Society Mishra, N. K., Mandava, P., Chen, C., Grotta, J., Lees, K. R., Kent, T. A. 2013

    Abstract

    The National Institutes of Neurological Disorders and Stroke and the European Co-operative Acute Stroke III trials enrolled a largely Caucasian population, but the results are often extrapolated onto non-Caucasians. A limited number of nonrandomized studies have proposed that non-Caucasian patients show differential response to tissue plasminogen activator.We examined if non-Caucasian patients of mixed national origin within the Virtual International Stroke Trials Archives neuroprotection trials responded differently to tissue plasminogen activator compared with Caucasians.We matched patients within each race-subtype for age, baseline National Institutes of Health Stroke Scales, and diabetes status, and excluded outliers. We tested for an interaction of race ethnicity with tissue plasminogen activator on predicting outcomes at α = 0·05. We compared 90-day ordinal outcome (modified Rankin Scale; primary analysis) and dichotomized outcomes (modified Rankin Scale 0-1; modified Rankin Scale 0-2; survival) within individual race ethnicity.One thousand nine hundred forty-six thrombolysed patients (125 Blacks, 39 Asians, and 1821 Caucasians) were matched with 1946 non-thrombolysed patients in each race ethnicity group. Postmatching, there were no imbalances in baseline National Institutes of Health Stroke Scales and age between the groups (P > 0·05). The interaction of tissue plasminogen activator with race ethnicity was nonsignificant in ordinal (P = 0·4) and in dichotomized outcome models (P > 0·05). Ordinal odds for improved outcomes were 1·5 for all patients (P < 0·05). Ordinal odds for Caucasians were 1·5 (P < 0·05); for Blacks, 2·1 (P < 0·05); and for Asians, 1·2 (P > 0·05; 1·6 after 1:2 matching with nonthrombolysed, because of small numbers). Dichotomized functional outcomes improved after thrombolysis overall, in Caucasians, in Blacks (modified Rankin Scale 0-2 only), and in Asians (after 1:2 matching; P > 0·05). Odds for survival were consistent across all groups.These results do not suggest a differential response to tissue plasminogen activator based on race ethnicity. Among Asians, data were particularly sparse, and results should be interpreted with caution.

    View details for DOI 10.1111/ijs.12162

    View details for PubMedID 24148895

  • Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus NEUROLOGY Mishra, N. K., Ahmed, N., Davalos, A., Iversen, H. K., Melo, T., Soinne, L., Wahlgren, N., Lees, K. R. 2011; 77 (21): 1866-1872

    Abstract

    Patients with concomitant diabetes mellitus (DM) and prior stroke (PS) were excluded from European approval of alteplase in stroke. We examined the influence of DM and PS on the outcomes of patients who received thrombolytic therapy (T; data from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) compared to nonthrombolyzed controls (C; data from Virtual International Stroke Trials Archive).We selected ischemic stroke patients on whom we held data on age, baseline NIH Stroke Scale score (NIHSS), and 90-day modified Rankin Scale score (mRS). We compared the distribution of mRS between T and C by Cochran-Mantel-Haenszel (CMH) test and proportional odds logistic regression, after adjustment for age and baseline NIHSS, in patients with and without DM, PS, or the combination. We report odds ratios (OR) for improved distribution of mRS with 95% confidence interval (CI) and CMH p value.Data were available for 29,500 patients: 5,411 (18.5%) had DM, 5,019 had PS (17.1%), and 1,141 (5.5%) had both. Adjusted mRS outcomes were better for T vs C among patients with DM (OR 1.45 [1.30-1.62], n = 5,354), PS (OR 1.55 [1.40-1.72], n = 4,986), or concomitant DM and PS (OR 1.23 [0.996-1.52], p = 0.05, n = 1,136), all CMH p < 0.0001. These are comparable to outcomes between T and C among patients with neither DM nor PS: OR = 1.53 (1.42-1.63), p < 0.0001, n = 19,339. There was no interaction on outcome between DM and PS with alteplase treatment (tissue plasminogen activator × DM × PS, p = 0.5). Age ?80 years or >80 years did not influence our findings.Outcomes from thrombolysis are better than the controls among patients with DM, PS, or both. We find no statistical justification for the exclusion of these patients from receiving thrombolytic therapy.

    View details for DOI 10.1212/WNL.0b013e318238ee42

    View details for Web of Science ID 000297322600012

    View details for PubMedID 22094479

  • Low Body Temperature Does Not Compromise the Treatment Effect of Alteplase STROKE Lees, J. S., Mishra, N. K., Saini, M., Lyden, P. D., Shuaib, A. 2011; 42 (9): 2618-2621

    Abstract

    Hypothermia is neuroprotective in ischemic stroke models. The influence of baseline body temperature on outcomes after thrombolytic therapy is unclear. We examined outcomes after alteplase treatment across baseline body temperature for patients with ischemic stroke in data held within the Virtual International Stroke Trials Archive (VISTA; 1998 to 2007).We collated data on age, baseline severity (National Institutes of Health Stroke Scale), and 90-day modified Rankin Scale score on patients presenting with acute ischemic stroke. We compared 90-day modified Rankin Scale score between thrombolyzed and nonthrombolyzed comparators across baseline body temperature. We report age and baseline National Institutes of Health Stroke Scale-adjusted Cochran-Mantel-Haenszel probability value and proportional OR with 95% CI for improved modified Rankin Scale distribution. We report temperature profiles over 72 hours after stroke by treatment group.Rankin data were available for 5586 patients with acute ischemic stroke in VISTA (1980 received alteplase). Age and baseline severity were similar (age 68.0±13.0 years versus 69.9±12.3 years, National Institutes of Health Stroke Scale 14.2±5.2 versus 13.0±5.6). Alteplase was associated with improved outcome (OR, 1.49; 95% CI, 1.35 to 1.65, P<0.0001). Alteplase treatment effect was not associated with baseline temperature (P=0.14). Point estimates showed benefit of alteplase treatment across 35.5°C to 37.5°C but showed a negative trend >37.5°C. Alteplase did not influence temperature profiles over 72 hours after stroke.There is no evidence of influence of body temperature on alteplase treatment response. These results are reassuring that low temperatures across a physiological range do not compromise therapeutic effect of alteplase.

    View details for DOI 10.1161/STROKEAHA.110.611210

    View details for Web of Science ID 000294342800053

    View details for PubMedID 21757664

  • Home Time Is Extended in Patients With Ischemic Stroke Who Receive Thrombolytic Therapy A Validation Study of Home Time as an Outcome Measure STROKE Mishra, N. K., Shuaib, A., Lyden, P., Diener, H., Grotta, J., Davis, S., Davalos, A., Ashwood, T., Wasiewski, W., Lees, K. R. 2011; 42 (4): 1046-1050

    Abstract

    "Home time" (HT) refers to the number of days over the first 90 after stroke onset that a patient spends residing in their own home or a relative's home versus any institutional care. It is an accessible and objective parameter, free from subjective bias, with potential as an outcome measure in acute stroke trials. We sought to validate HT and assess treatment responsiveness using independent data.We estimated HT in the Stroke Acute Ischemic NXY Treatment (SAINT) I neuroprotection trial. We compared outcomes between thrombolyzed (T) and nonthrombolyzed comparators (C) using HT and the modified Rankin Scale. For our primary analysis, we adjusted for baseline covariates that significantly influence HT and in sensitivity analyses considered all variables that differed between groups at baseline. We report ordinal logistic regression and analysis of covariance with 95% CIs. We describe the relationship of HT with baseline National Institutes of Health Stroke Scale and its components and with Day 90 modified Rankin Scale and Barthel Index.SAINT I included 1699 patients from 23 countries, of whom 28.7% received alteplase. HT correlated with age, baseline severity, alteplase use, side of ischemic lesion, presence of diabetes, and country of patient enrollment (each P<0.05). We found an association between use of alteplase with better adjusted outcomes by either measure (OR for extended HT, 1.36; 95% CI, 1.08 to 1.72; P=0.009; analysis of covariance P=0.007 with a 5.5-day advantage; OR for more favorable modified Rankin Scale, 1.6; 95% CI, 1.28 to 2.00; P<0.0001; Cochran-Mantel-Haenszel P=0.046). HT was significantly associated with baseline National Institutes of Health Stroke Scale and each component of the National Institutes of Health Stroke Scale except level of consciousness, dysarthria, and ataxia. HT was significantly associated with Day 90 modified Rankin Scale and Barthel Index.HT is a responsive measure for use in multinational acute stroke trials. Its inclusion as a complementary outcome is reasonable. We propose treatment effects are adjusted for age, baseline National Institutes of Health Stroke Scale, side of stroke lesion, country of enrollment, and the presence of diabetes.

    View details for DOI 10.1161/STROKEAHA.110.601302

    View details for Web of Science ID 000288857200041

    View details for PubMedID 21350199

  • Low Body Temperature Does Not Significantly Compromise Therapeutic Effect of Alteplase STROKE Lees, J. S., Mishra, N. K., Saini, M., Lyden, P. D., Shuaib, A. 2011; 42 (3): E312-E312
  • Home Time Is Extended In Ischemic Stroke Patients Who Receive Thrombolytic Therapy: A Validation Study Of Home Time As An Outcome Measure STROKE Mishra, N. K., Shuaib, A., Lyden, P., Diener, H., Grotta, J., Davis, S., Davalos, A., Ashwood, T., Wasiewski, W., Lees, K. 2011; 42 (3): E245-E246
  • Mutism and Amnesia following High-Voltage Electrical Injury: Psychogenic Symptomatology Triggered by Organic Dysfunction? EUROPEAN NEUROLOGY Mishra, N. K., Russmann, H., Granziera, C., Maeder, P., Annoni, J. 2011; 66 (4): 229-234

    Abstract

    Mutism and dense retrograde amnesia are found both in organic and dissociative contexts. Moreover, dissociative symptoms may be modulated by right prefrontal activity. A single case, M.R., developed left hemiparesis, mutism and retrograde amnesia after a high-voltage electric shock without evidence of lasting brain lesions. M.R. suddenly recovered from his mutism following a mild brain trauma 2 years later.M.R.'s neuropsychological pattern and anatomoclinical correlations were studied through (i) language and memory assessment to characterize his deficits, (ii) functional neuroimaging during a standard language paradigm, and (iii) assessment of frontal and left insular connectivity through diffusion tractography imaging and transcranial magnetic stimulation. A control evaluation was repeated after recovery.M.R. recovered from the left hemiparesis within 90 days of the accident, which indicated a transient right brain impairment. One year later, neurobehavioral, language and memory evaluations strongly suggested a dissociative component in the mutism and retrograde amnesia. Investigations (including MRI, fMRI, diffusion tensor imaging, EEG and r-TMS) were normal. Twenty-seven months after the electrical injury, M.R. had a very mild head injury which was followed by a rapid recovery of speech. However, the retrograde amnesia persisted.This case indicates an interaction of both organic and dissociative mechanisms in order to explain the patient's symptoms. The study also illustrates dissociation in the time course of the two different dissociative symptoms in the same patient.

    View details for DOI 10.1159/000330953

    View details for Web of Science ID 000295363700010

    View details for PubMedID 21952143

  • Comparison of Outcomes Following Thrombolytic Therapy Among Patients With Prior Stroke and Diabetes in the Virtual International Stroke Trials Archive (VISTA) DIABETES CARE Kumar, N., Davis, S. M., Kaste, M., Lees, K. R. 2010; 33 (12): 2531-2537

    Abstract

    The use of alteplase in patients who have had a prior stroke and concomitant diabetes is not approved in Europe. To examine the influence of diabetes and prior stroke on outcomes, we compared data on thrombolysed patients with nonthrombolysed comparators.We selected patients with ischemic stroke on whom we had data on age, pretreatment baseline National Institutes of Health Stroke Scale (b-NIHSS), and 90-day outcome measures (functional modified Rankin score [mRS]) and neurological measures [NIHSS]) in the Virtual International Stroke Trials Archive. We compared outcomes between thrombolysed patients and nonthrombolysed comparators in those with and without diabetes, those who have had a prior stroke, or both and report findings using the Cochran-Mantel-Haenszel (CMH) test and proportional odds logistic regression analyses. We report an age-adjusted and b-NIHSS-adjusted CMH P value and odds ratio (OR).Rankin data were available for 5,817 patients: 1,585 thrombolysed patients and 4,232 nonthrombolysed comparators. A total 1,334 (24.1%) patients had diabetes, 1,898 (33.7%) patients have had a prior stroke, and 491 (8%) patients had both. Diabetes and nondiabetes had equal b-NIHSS (median 13; P = 0.3), but patients who have had a prior stroke had higher b-NIHSS than patients who have not had a prior stroke (median 13 vs. 12; P < 0.0001). Functional outcomes were better for thrombolysed patients versus nonthrombolysed comparators among both nondiabetic (P < 0.0001; OR 1.4 [95% CI 1.3-1.6]) and diabetic (P = 0.1; 1.3 [1.05-1.6 ]) subjects. Similarly, outcomes were better for thrombolysed patients versus nonthrombolysed comparators among who have not had a prior stroke (P < 0.0001; 1.4 [1.2-1.6 ]) and those who have (P = 0.02; 1.3 [1.04-1.6 ]). There was no interaction of diabetes and prior stroke with treatment (P = 0.8). Neurological outcomes were consistent with the mRS.Outcomes from thrombolysis are better among patients with diabetes and/or those who have had a prior stroke than in control subjects. Withholding thrombolytic treatment from otherwise-eligible patients may not be justified.

    View details for DOI 10.2337/dc10.1125

    View details for Web of Science ID 000285666200008

    View details for PubMedID 20843977

  • Influence of Age on Outcome From Thrombolysis in Acute Stroke A Controlled Comparison in Patients From the Virtual International Stroke Trials Archive (VISTA) STROKE Mishra, N. K., Diener, H., Lyden, P. D., Bluhmki, E., Lees, K. R. 2010; 41 (12): 2840-2848

    Abstract

    Thrombolysis for acute ischemic stroke in patients aged > 80 years is not approved in some countries due to limited trial data in the very elderly. We compared outcomes between thrombolysed and nonthrombolysed (control) patients from neuroprotection trials to assess any influence of age on response. Method-Among patients with ischemic stroke of known age, pretreatment severity (baseline National Institutes of Health Scale Score), and 90-day outcome (modified Rankin Scale score; National Institutes of Health Scale score), we compared the distribution of modified Rankin score in thrombolysed patients with control subjects by Cochran-Mantel-Haenszel test and then logistic regression after adjustment for age and baseline National Institutes of Health Scale score. We examined patients ? 80 and ? 81 years separately and then each age decile.Rankin data were available for 5817 patients, 1585 thrombolysed and 4232 control subjects; 20.5% were aged > 80 years (mean ± SD, 85.1 ± 3.4 years). Baseline severity was higher among thrombolysed than control subjects (median National Institutes of Health Scale score 14 versus 13, P < 0.05). The distribution of modified Rankin Scale scores was better among thrombolysed patients (P < 0.0001; OR, 1.39; 95% CI, 1.26 to 1.54). The association occurred independently with similar magnitude among young (P < 0.0001; OR, 1.42; 95% CI, 1.26 to 1.59) and elderly (P = 0.002; OR, 1.34; 95% CI, 1.05 to 1.70) patients. ORs were consistent across all age deciles > 30 years; outcomes assessed by National Institutes of Health Scale score gave supporting significant findings, and dichotomized modified Rankin Scale score outcomes were also consistent.Outcome after thrombolysis for acute ischemic stroke was significantly better than in control subjects. Despite the expected poorer outcomes among elderly compared with young patients that is independent of any treatment effect, the association between thrombolysis treatment and improved outcome is maintained in the very elderly. Age alone should not be a barrier to treatment.

    View details for DOI 10.1161/STROKEAHA.110.586206

    View details for Web of Science ID 000284685600027

    View details for PubMedID 21030710

  • Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive BRITISH MEDICAL JOURNAL Mishra, N. K., Ahmed, N., Andersen, G., Egido, J. A., Lindsberg, P. J., Ringleb, P. A., Wahlgren, N. G., Lees, K. R. 2010; 341

    Abstract

    To assess effect of age on response to alteplase in acute ischaemic stroke.Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA).23?334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29?500 patients (3472 aged >80 ("elderly," mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29?228 patients for analysis adjusted for age and baseline severity.Functional outcomes at 90 days measured by score on modified Rankin scale.Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29?228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ?80 (1.6, 1.5 to 1.7; P<0.001; n=25?789) and in those aged >80 (1.4, 1.3 to 1.6; P<0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis.Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.

    View details for DOI 10.1136/bmj.c6046

    View details for Web of Science ID 000284830900032

    View details for PubMedID 21098614

  • 5th UK Stroke Forum Conference 30 November-2 December 2010 SECC, Glasgow, UK Abstracts INTERNATIONAL JOURNAL OF STROKE Mishra, N. K., Lees, K. R., Wahlgren, N., Ahmed, N., Anderson, G., Bluhmki, E., Davalos, A., Davis, S., Diener, H., Grotta, J., Egido, J., Klingenberg, H., Kaste, M., Kobayashi, A., Kaell, T., Lindsberg, P., Lyden, P., Ringleb, P., Soinne, L. 2010; 5: 3-67
  • Thrombolysis Is Associated With Consistent Functional Improvement Across Baseline Stroke Severity A Comparison of Outcomes in Patients From the Virtual International Stroke Trials Archive (VISTA) STROKE Mishra, N. K., Lyden, P., Grotta, J. C., Lees, K. R. 2010; 41 (11): 2612-2617

    Abstract

    Baseline stroke severity predicts outcomes among thrombolysed patients. The baseline National Institutes of Health Stroke Scale (NIHSS) thresholds are sometimes used to select patients for thrombolysis, clinical trial enrollment, or both. Using data lodged with Virtual International Stroke Trials Archive, we compared adjusted outcomes between thrombolysed and nonthrombolysed patients enrolled in neuroprotection trials (1998-2007) to assess the influence of various levels of baseline NIHSS. Method-We assessed the association of treatment with outcome, measured across the modified Rankin scale score distribution, in patients categorized by baseline NIHSS in increments of 4. We used an age and baseline NIHSS adjusted Cochran-Mantel-Haenszel test followed by proportional odds logistic regression analysis. We report the Cochran-Mantel-Haenszel P values and estimated odds ratios (OR) for improved modified Rankin scale score distribution with treatment for patients within each baseline NIHSS category.Data were available for 5817 patients (1585 thrombolysed and 4232 nonthrombolysed). Baseline severity was greater among thrombolysed than nonthrombolysed (median baseline NIHSS, 14 vs 13; P < 0.05). An association of treatment with outcome was seen independently and was of similar magnitude within each of the baseline NIHSS categories 5 to 8 (P=0.04; OR, 1.25; 95% confidence interval [CI], 1.0-1.6; N = 278/934 thrombolysed/nonthrombolysed), 9 to 12 (P = 0.01; OR, 1.3; 95% CI, 1.1-1.6; N = 404/942), 13 to 16 (P < 0.05; OR, 1.6; 95% CI, 1.3-2.1; N = 342/814), 17 to 20 (P < 0.05; OR, 1.7; 95% CI, 1.3-2.1; N = 311/736), and 21 to 24 (P < 0.05; OR, 1.6; 95% CI, 1.1-2.1; N = 178/466). No association was observed within baseline NIHSS categories 1 to 4 (P = 0.8; OR, 1.1; 95% CI, 0.3-4.4; N = 8/161) or ? 25 (P = 0.08; OR, 1.1; 95% CI, 0.7-1.9; N = 64/179).In this nonrandomized comparison, outcomes after thrombolysis were significantly better than in untreated comparators across baseline NIHSS 5 to 24. The significant association was lost only at extremes of baseline NIHSS when sample sizes were small and confidence limits were wide.

    View details for DOI 10.1161/STROKEAHA.110.589317

    View details for Web of Science ID 000283443500048

    View details for PubMedID 20947852

  • Thrombolysis is Associated With Improved Outcome in Elderly Stroke Patients: A Non-randomized Comparison of Outcomes Amongst Patients From the Virtual International Stroke Trials Archive (VISTA) STROKE Mishra, N. K., Diener, H., Lyden, P., Lees, K. R. 2010; 41 (4): E208-E209
  • Mismatch-Based Delayed Thrombolysis A Meta-Analysis STROKE Mishra, N. K., Albers, G. W., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Lees, K. R. 2010; 41 (1): E25-E33

    Abstract

    Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I(2) (inconsistency), and L'Abbé plot.We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I(2)=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I(2)=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I(2)=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I(2)=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I(2)=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I(2)=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I(2)=0%).Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.

    View details for DOI 10.1161/STROKEAHA.109.566869

    View details for Web of Science ID 000273093400041

    View details for PubMedID 19926836

  • Stroke program for India ANNALS OF INDIAN ACADEMY OF NEUROLOGY Mishra, N. K., Khadilkar, S. V. 2010; 13 (1): 28-32

    Abstract

    India is silently witnessing a stroke epidemic. There is an urgent need to develop a national program towards "Fighting Stroke". This program should be specific to our national needs. In order to recommend on who should lead an Indian fight-stroke program, we examined the published opinions of stroke clinicians and the official documents on stroke care training abroad. We identified the resources that already exist in India and can be utilized to develop a national fight-stroke program. Through a review of published literature, we noted different opinions that exist on who would best manage stroke. We found that because stroke is a cardiovascular disorder of the central nervous system, its management requires a multi-disciplinary approach involving clinicians with background not limited to neurology. India has very few neurologists trained in stroke medicine and they cannot care for all stroke patients of the country. We propose a mechanism that would quickly put in place a stroke care model relevant in Indian context. We recommend for tapping the clinical expertise available from existing pool of non-neurologist physicians who can be trained and certified in stroke medicine (Strokology). We have discussed an approach towards developing a national network for training and research in Strokology hoping that our recommendations would initiate discussion amongst stroke academicians and motivate the national policy makers to quickly develop an "Indian Fight Stroke Program."

    View details for DOI 10.4103/0972-2327.61273

    View details for Web of Science ID 000208734000006

  • Recurrent Wernicke's Aphasia: Migraine and Not Stroke! HEADACHE Mishra, N. K., Rossetti, A. O., Menetrey, A., Carota, A. 2009; 49 (5): 765-768

    Abstract

    We report the clinical findings of a 40-year-old woman with recurrent migraine presenting with Wernicke's aphasia in accordance with the results of a standardized battery for language assessment (Boston Aphasia Diagnostic Examination). The patient had no evidence of parenchymal or vascular lesions on MRI and showed delta and theta slowing over the left posterior temporal leads on the EEG. Although the acute onset of a fluent aphasia suggested stroke as a likely etiology, the recurrence of aphasia as the initial symptom of migraine was related to cortical spreading depression and not to stroke.

    View details for Web of Science ID 000265550100018

    View details for PubMedID 19456883

  • Lifetime basilar migraine: A pontine syndrome? HEADACHE Mishra, N. K., Cereda, C., Carota, A. 2008; 48 (3): 476-478

    Abstract

    We describe the clinical and radiological findings of an 82-year-old woman patient with basilar type migraine attacks occurring over 70 years with a similar pattern of intensity and symptoms. We provide some evidence to suggest that gradual development of calcifications in the pontine tegmental nuclei can trigger attacks of basilar type migraine.

    View details for Web of Science ID 000253478300021

    View details for PubMedID 18081824

  • Poststroke hallucination delusion syndrome JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES Mishra, N. K., Hastak, S. 2008; 20 (1): 116-116

    View details for Web of Science ID 000253311000024

    View details for PubMedID 18305304

  • A squint of brain: A Capgras syndrome variant JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES Carota, A., Mishra, N., Allaoua, M., Ghika, J. 2008; 20 (1): 109-110

    View details for Web of Science ID 000253311000018

    View details for PubMedID 18305297

  • Antithrombotic agents in cerebral ischaemia. journal of the Association of Physicians of India Dalal, P. M., Mishra, N. K., Bhattacharjee, M., Bhat, P. 2006; 54: 555-561

    Abstract

    The current evidence suggests that aspirin is treatment of choice when compared to anticoagulants for patients with non-cardioembolic stroke. The usefulness of combination therapy (aspirin vs. with or without warfarin) is still debated. Likewise the combination of Aspirin with clopidogrel has no added advantage (MATCH Trial). However anticoagulant therapy significantly benefits high-risk patients with atrial fibrillation in the elderly subjects whereas aspirin may still be the drug of choice in stroke prevention in low risk group in the younger age. There is dire need for well planned randomized double blind controlled studies to define the role of Antithrombotic agents in "cryptogenic stroke" (PFO/ASD related) antiphospholipid antibody syndrome, arterial dissections and intraluminal clot syndromes. Evaluation and treatment of associated risk factors in all categories needs greater emphasis.

    View details for PubMedID 17089906

  • Comprehensive stroke care: an overview. journal of the Association of Physicians of India Mishra, N. K., Patel, H., Hastak, S. M. 2006; 54: 36-41

    Abstract

    Stroke is a global epidemic and an important cause of morbidity and mortality. It ranks next to cardiovascular disease and cancer as a cause of death. "India is likely to suffer huge social and economic burden in the rehabilitation of stroke patients owing to increased life expectancy" and urbanization. Though, there are national programs in malaria eradication and tuberculosis control, there is hardly any governmental support in stroke management and rehabilitation. We propose to formulate stroke-prevention strategies specific to our national needs and covering all the age groups. Allocation of resources towards the stroke management and research is needed. Emphasis on stroke awareness in community should be stressed and should be inclusive of means of primordial and primary prevention apart from management of stroke and its recurrence. Recent international experience in stroke management has suggested the need of specialized stroke units (comprehensive stroke care under one roof). We wish to establish the need of creating awareness regarding the urgency of specialized care in acute stroke. We also wish to motivate our national health institutions to offer affordable, evidence based management of stroke and offer opportunities in stroke training and research.

    View details for PubMedID 16649738

  • Abulia: no will, no way. journal of the Association of Physicians of India Hastak, S. M., Gorawara, P. S., Mishra, N. K. 2005; 53: 814-818

    Abstract

    Abulia refers to impaired ability to perform voluntary actions, show initiative, make decisions along with decrease in movements, speech, thought and emotional reactions. We describe here two patients who developed this condition following bilateral insult to different sites in the centromedial core of the brain, the first following the cerebral venous thrombosis and the second after the right ACA and MCA infarct. Both these patients improved following treatment with Bromocriptine. These cases are described for proper identification and management by the clinicians.

    View details for PubMedID 16334629

Stanford Medicine Resources: